Top-down Fabrication of PEG-NHC Stabilized Gold Nanoparticles Bearing Azides Functional Groups

18 April 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Swift and accurate biochemical marker detection is crucial for medical diagnosis. Gold nanoparticles (AuNPs) are promising for such diagnostic sensing due to their biocompatibility and unique physical properties. However, AuNPs bearing selective targeting vectors often lack prolonged stability in complex analytes. To enhance stability, (N)-heterocyclic carbene (NHC) ligands have been explored due to their strong binding to AuNP surfaces. This study presents an optimization path towards the general top-down synthesis of highly stable, azide-terminal PEGylated NHC (PEG-NHC) functionalized AuNPs using well-defined oleylamine-protected AuNPs and masked PEGylated NHC precursors. Furthermore, the activation and attachment mechanism of masked NHCs was elucidated by the identification of intermediate AuNPs obtained by insufficient ligand exchange. PEG-NHC@AuNPs retain colloidal stability in a range of biologically relevant media, showing no significant aggregation or ripening over a prolonged period and show greater stability when compared to the same particles synthesized via a bottom-up approach. Azide-functionalized PEG-NHC@AuNPs were further conjugated using a copper-catalyzed click- and a biorthogonal strain-promoted azide-alkyne cycloaddition reaction. The retained colloidal stability and the successful conjugation demonstrates the potential of azide-functionalized PEG-NHC@AuNP particles as a versatile platform for biomedical applications.


N-heterocyclic carbenes
NHC-stabilized gold nanoparticles
Click reaction
Biorthogonal conjugation

Supplementary materials

Supporting Information
Synthesis details, NMR, XPS and FT-IR spectra comparisons of all AuNPs obtained by different procedures P1-P4 and their precursor structures. Synthesis details, NMR (1H and 13C) and MS (Maldi-TOF) spectra for molecular compounds. NMR spectra (1H, 13C and 1H/13C HMBC), high-resolution XPS data, TEM micrographs, UV-Vis, DLS, TGA and stability studies of PEGylated NHC@AuNPs. ‘Click’ conjugation procedures and characterization of conjugated AuNPs.


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